This invention relates to substituted pyridoindole anti-depressants.
Clin-Midy, in British Pat. No. 1,382,943 and CanasRodriquez & Leeming in British Pat. No. 1,220,628 disclose various intermediates used in the preparation of compounds of this invention.
Duschinsky, in U.S. Pat. No. 2,642,438 discloses 9-aryl-2-substituted-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indoles useful as spasmolytics and adrenolytics, and 1-phenyl-3-(.beta.-aminoethyl)indole and its derivatives which are intermediates in the preparation of compounds of this invention. These intermediates are also disclosed in J. Pharm. Sci. 57: 1364-69 (1968).
Mental illness encompasses both psychoses and neuroses. Symptoms requiring treatment include depression, anxiety, agitation, and hallucinations. Among the drugs used particularly for treatment of both reactive and endogenous depressions are monoamine oxidase (MAO) inhibitors, such as iproniazide, tranylcypromine, nialamide, phenelzine, and pargyline, and the non-MAO-inhibiting tricyclic aromatic dibenzazepines, such as imipramine, and dibenzocycloheptenes such as amitriptyline.
All of these drugs have adverse side effects that limit their usefulness. MAO inhibitors may benefit milder forms of depression, but the risk of serious toxic effects is a strong argument against their use. They can cause liver damage and acute hypertension, especially if given in conjunction with cheese, bananas, or other amine-containing foods. The MAO inhibitors can also cause tremors, insomnia, hyperhydrosis, agitation, hypermanic behavior, confusion, hallucinations, convulsions and orthostatic hypotension. They frequently cause dizziness, vertigo, headache, inhibition of ejaculation, difficulty in urination, weakness, fatique, dry mouth, constipation and blurred vision.
Imipramine can cause blurred vision, dryness of mouth, constipation, urinary retention, orthostatic hypotension, respiration depression, myocardial infarction, and congestive heart failure. Similar difficulties are experienced with amitriptyline.
There is a continuing need for psychotherapeutic agents that have fewer side effects than the drugs in use today; also for psychotherapeutic agents that have different modes of action than presently used agents, since none of these is completely effective.
The present invention results from efforts to develop new, safe, and effective psychotherapeutic compounds with minimal side effects.